Cancer is a leading cause of death worldwide. Survival rates for many cancers can be improved by early detection and treatment. However, for many cancers, diagnostic approaches are highly invasive, for example, involving surgical biopsy. Less invasive methods, such as needle biopsies, are often less reliable. More reliable methods of cancer detection are desired, as are less invasive methods of detection.
Midkine, also known as MK, MDK, and NEGF2, is a 13-kDa heparin-binding growth factor rich in basic amino acids and cysteine which affects growth, survival, migration, and gene expression of various target cells. Human midkine is encoded by the MDK gene. Expression of the MDK gene is induced by retinoic acid or hypoxia, and suppressed by glucocorticoid. Expression of MDK is high during midgestation, but low or absent in most adult tissues (Muramatsu et al., Proc. Jpn. Acad., Ser. B, 86: 410-425 (2010)).
MDK gene expression is increased in Wilms' tumor specimens and in human stomach, colon, pancreatic, lung, and esophageal carcinoma cell lines (Tsutsui et al., Cancer Res., 53: 1281-1285 (1993)). Serum levels of midkine are increased in patients with esophageal, gastric, duodenal, colon, hepatocellular, bile duct/gallbladder, pancreatic, thyroid, or lung carcinoma (Ikematsu et al., Brit. J. Cancer, 83(6): 701-706 (2000)). In situ hybridization and immunohistochemical analyses demonstrated that MDK expression and midkine production are increased in human thyroid papillary carcinoma specimens (Kato et al., Mod. Pathol., 13(10): 1060-1065 (2000)).
Improved methods, compositions, and kits for detecting midkine expression in a biological sample are desired, which may be useful for diagnostic and prognostic purposes in proliferative disorders, such as cancer.